The work of breathing is a major determinant of the success of weaning from mechanical ventilation. The aim of this study was to assess whether an inhaled bronchodilator could reduce the mechanical load on the respiratory muscles and diminish the work. For this purpose, 15 intubated patients in the process of weaning from mechanical ventilation inhaled the β2-agonist bronchodilator albuterol via a spacer device filled with 1 mg of the drug and connected to the endotracheal tube. During spontaneous breathing, the mean work of breathing diminished significantly after albuterol, from 9.35 ± 1.05 to 8.33 ± 1.13 J/min (p < 0.01), and seven patients exhibited a decrease superior or equal to 15%. This decrease resulted from a marked reduction in lung and airway resistance, from 12.0 ± 1.7 to 9.8 ± 1.4 cm H2O·L−1·s (p < 0.05). No significant changes were observed in the breathing pattern, intrinsic PEEP or arterial blood gas measurements after albuterol, and peripheral cardiovascular effects were not significant. In seven patients, we were able to compare the changes that occurred after albuterol in the work of breathing during weaning from mechanical ventilation with the changes in pulmonary function induced by albuterol after extubation, as assessed by the forced oscillation method. A close correlation was found between the two types of change, further indicating that the reduction in the work of breathing was more likely to occur in patients with the largest bronchodilating effect of albuterol at baseline. We propose to use this technique for patients who have difficulty in tolerating the cessation of mechanical ventilation as an aid to reducing the load on the respiratory muscles, especially when partial reversibility of airway obstruction is known or suspected.